A comprehensive study of the mechanisms by which the peptide hormones, angiotensin and bradykinin stimulate the release of prostaglandins from perfused organs offers a means of probing cellular regulation of prostaglandin metabolism. Peptide mediated release of prostaglandins is not observed with all isolated organ preparation suggesting a specific mechanism or site of action for the peptides. Not yet fully defined is the correlation between prostaglandin release and vascular activity of the peptide. We will synthesize analogs of these peptides, infuse them into several models, isolated organ preparations and determine the quantities and types of prostaglandins released. Prostaglandin release from any tissue reflects the net result of synthesis and degradation. To identify mechanisms by which peptides affect prostaglandin metabolism, we will isolate and characterize prostaglandin synthetase, phospholipase A2 and 15-OH PG dehydrogenase from both "responding" and "non-responding" tissues. One of our goals will be to identify those peptides (and other agents) whose primary physiological activity is mediated through the local release of prostaglandins. Since organ perfusion is one determinant of drug distribution, agents which stimulate the local release of prostaglandins, may enhance selective toxicity of cytotoxic drugs.